The broad and long term objective of this proposal is to synthesize the natural product fleephilone in order to elucidate how fleephilone inhibits REV/RRE binding between the REV protein and mRNA in the HIV-1 Virus. Inhibition of REV/RRE binding is a viable target for a research program focused on the prevention of HIV-1 replication. Inhibition studies will be carried out using NMR techniques to study exactly how fleephilone interrupts binding. With a greater understanding of how fleephilone inhibits REV/RRE binding it is anticipated that more potent analogs of fleephilone can be synthesized in an effort to develop AIDS drugs targeting REV/RRE binding. The specific aims of the proposal are to synthesize the natural product fleephilone using techniques in organic synthetic chemistry. The total synthesis of fleephilone will also allow for the determination of the absolute and relative stereochemistry of the molecule.